PURPOSE: This study aimed to investigate the relationship of physical activity levels on white matter volume in post-9/11 Veterans. METHODS: The study consisted of post-9/11 Veterans enrolled in the Translational Research Center for TBI and Stress Disorders (TRACTS) longitudinal study at VA Boston Healthcare System. Participants were retrospectively categorized into two groups: a Vigorous group of Veterans who participated in vigorous-intensity physical activity (n = 84), and a No Vigorous group of Veterans who reported no participation of vigorous-intensity physical activity (n = 62). Physical activity was measured using the International Physical Activity Questionnaire (IPAQ), and Veterans underwent quantitative brain magnetic resonance imaging (MRI) to obtain regional white matter volumes. RESULTS: A cross-sectional analysis revealed trends of greater white matter volume throughout brain regions associated with cognitive functions and emotional regulation in the Vigorous group compared to the No Vigorous group. Following correction for multiple comparison, significant differences between groups were found in the right [p-corrected = 0.049] and left [ p-corrected = 0.049] precuneus. Furthermore, an interaction analysis showed that the difference in white matter volume between vigorous and non-vigorous activity groups was more pronounced in individuals with PTSD compared to those without PTSD. CONCLUSIONS: These data offer new insights suggesting vigorous physical activity is associated with neural benefits in Veterans with PTSD.